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Exploring the Tumor Microenvironment with Nanoparticles

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Nanotechnology-Based Precision Tools for the Detection and Treatment of Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 166))

Abstract

Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. While enhanced permeability and retention effect (EPR) promotes nanoparticle (NP) extravasation, the abnormal tumor vasculature, high interstitial pressure and dense stroma structure limit homogeneous intratumoral distribution of NP and compromise their imaging and therapeutic effect. Moreover, heterogeneous distribution of NP in nontumor-stroma cells damages the nontumor cells, and interferes with tumor-stroma crosstalk. This can lead to inhibition of tumor progression, but can also paradoxically induce acquired resistance and facilitate tumor cell proliferation and metastasis. Overall, the tumor microenvironment plays a crucial, yet controversial role in regulating NP distribution and their biological effects. In this review, we summarize recent studies on the stroma barriers for NP extravasation, and discuss the consequential effects of NP distribution in stroma cells. We also highlight design considerations to improve NP delivery and propose potential combinatory strategies to overcome acquired resistance induced by damaged stroma cells.

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Abbreviations

EPR:

Enhanced Permeability and Retention Effect

ECM:

Extracellular Matrix

TME:

Tumor Microenvironment

BM:

Basement Membrane

IFP:

Interstitial Fluidic Pressure

TAF:

Tumor Associated Fibroblast

TAM:

Tumor Associated Macrophage

MMP:

Matrix Metalloproteinases

NP:

Nanoparticles

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Acknowledgments

This work was supported by NIH grant support: CA149363, CA151652, CA149387 and DK100664. The authors thank Andrew Mackenzie Blair for his assistance in the chapter preparation.

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  1. Division of Molecular Pharmaceutics and Center of Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Lei Miao & Leaf Huang

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  1. Lei Miao
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  2. Leaf Huang
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Editors and Affiliations

  1. Department of Chemistry and International Institute for Nanotechnology, Northwestern University, Evanston, Illinois, USA

    Chad A. Mirkin

  2. Department of Chemistry and International Institute for Nanotechnology, Northwestern University, Evanston, Illinois, USA

    Thomas J. Meade

  3. Department of Chemistry and International Institute for Nanotechnology, Northwestern University, Evanston, Illinois, USA

    Sarah Hurst Petrosko

  4. Department of Neurology, Robert H. Lurie Comprehensive Cancer Center and International Institute for Nanotechnology, Northwestern University Robert H. Lurie Comp. Cancer Center, Chicago, Illinois, USA

    Alexander H. Stegh

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Miao, L., Huang, L. (2015). Exploring the Tumor Microenvironment with Nanoparticles. In: Mirkin, C., Meade, T., Petrosko, S., Stegh, A. (eds) Nanotechnology-Based Precision Tools for the Detection and Treatment of Cancer. Cancer Treatment and Research, vol 166. Springer, Cham. https://doi.org/10.1007/978-3-319-16555-4_9

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